Table 2.

Clinical studies on the value of cellular immune imbalances as drivers and predictors of outcomes in NAFLD.

Reference	Cellular biomarker	Number of patients	Results
Lee et al. (23)	WBC	3,681 healthy subjects who underwent medical checkup	The risk of NAFLD increased significantly as WBC increased. Compared with the lowest WBC count quartile, the respective ORs (95% CIs) for the second, third, and fourth quartiles were 1.48 (1.10–1.98), 1.59 (1.18–2.14), and 1.84 (1.35–2.51) for men; and 1.15 (0.67–1.96), 1.88 (1.13–3.11), and 2.74 (1.68–4.46) for women
Wang et al. (83)	WBC count	15,201 participants without NAFLD who underwent health checkups between 2005 and 2011	There were 3,376 new cases of NAFLD, and WBC count was a predictor of its incidence. Compared with the lowest WBC quartile (Q1), the HRs (95% CIs) were 1.09 (0.97–1.21), 1.17 (1.05–1.30), and 1.15 (1.03–1.28) for Q2, Q3, and Q4 quartiles, respectively, after adjusting for potential confounders
Alkhouri et al. (25)	NLR	101 patients with suspected NAFLD who underwent liver biopsy	Patients with NASH had a higher NLR than those without (median 2.5 vs. 1.6, P < 0.001). The NLR correlated with the NAFLD activity score and its individual components (steatosis, inflammation, and ballooning P < 0.001). Patients with advanced fibrosis (F3–4) had higher NLR than those in lower fibrosis stages (F1–2) (mean 2.9 vs. 1.8, P < 0.001). Each one-unit increase in NLR increased by 70 and 50% the likelihood of having NASH and fibrosis, respectively
Shahawy et al. (84)	NLR	90 subjects (30 with NASH, 30 with simple steatosis, and 30 healthy control)	NLR levels were significantly higher in NASH and simple steatosis groups compared to healthy controls (mean: 2.19, 1.55, and 1.19, respectively, P < 0.001)
Leithead et al. (72)	NLR	570 patients with end-stage cirrhosis (54 due to NAFLD) listed for liver transplantation	After adjusting for MELD, NLR ≥ 5 was associated with higher 3-month mortality (OR 6.02, P = 0.043). The proportion of patients who died by 3 months of listing was 3, 13.8, and 37.3% for NLR < 2, 2–4.9, and ≥5, respectively, P < 0.001. The listing NLR increased with increasing severity of ascites (median: 2.2, 3.1, and 4.6, for no ascites, controlled ascites, and refractory ascites, respectively, P < 0.001). NLR had positive correlation with listing serum bilirubin (r = 0.277, P < 0.001), listing INR (r = 0.156, P < 0.001), MELD score (r = 0.297, P < 0.001), and negative correlation with serum albumin (r = −0.090, P = 0.033), and serum sodium (r = −0.453, P < 0.001)
Yilmaz et al. (22)	NLR	102 patients (38 with NASH, 19 with HCV, and 45 with HBV) and 35 healthy controls	NLR was significantly higher in NASH patients compared to controls, HBV, and HCV patients (P < 0.001, P < 0.001, and P < 0.001, respectively); and was positively associated with NAFLD activity scores (r = 0.861, P < 0.001), liver fibrosis (β = 0.631, P < 0.001), and NASH (β = 0.753, P < 0.001)
Abdel-Razik et al. (71)	NLR	873 patients with biopsy-proven NAFLD (120 with NASH and 753 with simple steatosis) and 150 healthy controls	Patients with NASH had higher NLR than those without (mean: 2.6 vs. 1.9, respectively, P < 0.001). The NLR correlated positively with NAFLD activity score, pro-inflammatory cytokines, and CRP (P < 0.001). In addition, patients with advanced fibrosis stages (F3–4) had a higher NLR than those with mild (F1–2) (mean 2.5 vs.1.8, respectively, P < 0.001); with the highest specificity (79.2%) and sensitivity (69.4%) for identification of advanced fibrosis at NLR cutoff of 2.4 (AUC = 0.732, P < 0.001)
Rau et al. (30)	Th17 and the T regulatory cells	51 patients [30 with NASH and 31 with NAFLD (without histology)] and 43 healthy controls	Patients with NASH (and in less degree with steatosis) had a lower frequency of T regulatory cells in their peripheral blood, in comparison with controls. Progression from steatosis to NASH was marked by a higher frequency of Th17 cells in the liver, and an increased Th17/resting Treg ratio in the liver and in peripheral blood

NLR, neutrophil-to-lymphocyte ratio; WBC, white blood cell.